A Study to Compare Pharmacokinetics (PK) of Etrolizumab Administered Subcutaneously by a Prefilled Syringe With Needle Safety Device (PFS-NSD) or an Auto-injector (AI)

A Randomized, Open-Label, 2-Part, 2-Arm, Parallel-Group, Single-Dose, Multi-Center Study in Healthy Subjects to Investigate the Comparability of Pharmacokinetics of Etrolizumab Administered Subcutaneously by a Prefilled Syringe With Needle Safety Device or an Auto-Injector

This is a randomized, 2-part, 2-arm, open-label, parallel-group, multi-center study to compare the PK of etrolizumab administered subcutaneously by an AI (test device) or a PFS-NSD (reference device) in healthy participants. The study will comprise a pilot cohort (Part 1) to estimate the geometric mean ratio (GMR) and variability of the maximum observed concentration (Cmax) and area under the concentration-time curve (AUC) to confirm or determine the sample size for the pivotal cohort (Part 2). The pivotal cohort will demonstrate exposure comparability of Cmax, AUC from Hour 0 to the last measurable concentration (AUClast), and AUC from Hour 0 to extrapolated infinite time (AUC0-inf), values for a single dose of etrolizumab administered subcutaneously either by the AI or the PFS-NSD.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Etrolizumab; Device: Auto-Injector (AI); Device: Prefilled Syringe With Needle Safety Device (PFS-NSD)

• Study Type: Interventional
• Enrollment (Actual): 180
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • Covance Research Unit - Daytona
  • Indiana
    • Evansville, Indiana, United States, 47710
      • Covance Clinical Research Unit Inc.; Covance Gfi Research
  • Texas
    • Dallas, Texas, United States, 75247
      • Covance Research Unit - Dallas
  • Wisconsin
    • Madison, Wisconsin, United States, 53704
      • Covance Clinical Research Unit, Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Within the body weight range of 60 to 100 kilograms, inclusive (for the pivotal cohort [Part 2] only)
• Within body mass index (BMI) range 18.0 to 30.0 kilograms per square meter (kg/m^2), inclusive
• In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead electrocardiogram (ECG), and vital signs
• Females will be non-pregnant, non-lactating, and either postmenopausal (at least 12 months of non-therapy-induced amenorrhea)/surgically sterile (e.g., tubal ligation, hysterectomy) for at least 90 days prior to enrolment, or agree to remain abstinent/use a highly effective method of contraception for at least 24 weeks after study drug administration
• Males will either be sterile or agree to remain abstinent/use a highly effective method of contraception for at least 24 weeks after study drug administration. Male participants will refrain from sperm donation from Check-in (Day -1) until 24 weeks following study drug administration

Exclusion Criteria:

• Any prior treatment with etrolizumab or other anti-integrin agents (including natalizumab, vedolizumab, and efalizumab)
• Any prior treatment with anti-mucosal addressin cell adhesion molecule 1 (anti-MAdCAM-1) agents
• Any prior treatment with rituximab
• Received intravenous corticosteroids within 30 days prior to Screening
• Use of agents that deplete B or T cells (e.g., alemtuzumab, rituximab, or visilizumab) within 12 months prior to randomization
• Any prior immunosuppressive agents (including cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil)
• Chronic nonsteroidal anti-inflammatory drug (NSAID) use
• Use of any prescription medications/products within 14 days prior to Check in (Day -1)
• History of demyelinating disease
• Neurological conditions or diseases
• History of cancer
• History of alcoholism or drug addiction within less than (<) 1 year prior to Screening
• History of active or latent tuberculosis (TB), regardless of treatment history
• History of recurrent opportunistic infections and/or history of severe disseminated viral infections
• Positive for human immunodeficiency virus (HIV) antibody
• Any current or recent signs or symptoms of infection
• Pregnant or lactating
• Hospitalized within 4 weeks prior to and during Screening
• History of organ transplant
• Presence of skin rash at Screening or history of other skin disorders
• Tattoos, scars, chronic rashes, or sunburn in the area of the designated injection site

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Etrolizumab AI; Participants will receive a single dose of etrolizumab via subcutaneous (SC) injection using the AI on Day 1.	Drug: Etrolizumab; Etrolizumab will be administered at a dose of 105 milligrams (mg).; Other Names: RO5490261; Device: Auto-Injector (AI); The pre-filled AI will be used to administer etrolizumab.
Active Comparator: Part 1: Etrolizumab PFS-NSD; Participants will receive a single dose of etrolizumab via SC injection using the PFS-NSD on Day 1.	Drug: Etrolizumab; Etrolizumab will be administered at a dose of 105 milligrams (mg).; Other Names: RO5490261; Device: Prefilled Syringe With Needle Safety Device (PFS-NSD); The PFS-NSD will be used to administer etrolizumab.
Experimental: Part 2: Etrolizumab AI; Participants will receive a single dose of etrolizumab via SC injection using the AI on Day 1.	Drug: Etrolizumab; Etrolizumab will be administered at a dose of 105 milligrams (mg).; Other Names: RO5490261; Device: Auto-Injector (AI); The pre-filled AI will be used to administer etrolizumab.
Active Comparator: Part 2: Etrolizumab PFS-NSD; Participants will receive a single dose of etrolizumab via SC injection using the PFS-NSD on Day 1.	Drug: Etrolizumab; Etrolizumab will be administered at a dose of 105 milligrams (mg).; Other Names: RO5490261; Device: Prefilled Syringe With Needle Safety Device (PFS-NSD); The PFS-NSD will be used to administer etrolizumab.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Part 1: Cmax of Etrolizumab	Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71)
Part 1: AUClast of Etrolizumab	Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71)
Part 1: AUC0-inf of Etrolizumab	Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71)
Part 1: Ratio of AUClast to AUC0-inf (AUCR) of Etrolizumab	Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71)
Part 2: Cmax of Etrolizumab	Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71)
Part 2: AUClast of Etrolizumab	Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71)
Part 2: AUC0-inf of Etrolizumab	Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71)

Secondary Outcome Measures

Outcome Measure	Time Frame
Part 1: Time to Maximum Observed Concentration (tmax) of Etrolizumab	Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71)
Part 2: tmax of Etrolizumab	Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71)
Part 1: Apparent Terminal Elimination Half-Life (t1/2) of Etrolizumab	Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71)
Part 2: t1/2 of Etrolizumab	Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71)
Part 2: AUCR of Etrolizumab	Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71)
Percentage of Participants With Adverse Events	Part 1 and 2: Baseline up to Day 71
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) Against Etrolizumab	Part 1 and 2: Baseline up to Day 71

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Publications and helpful links

General Publications

• Zhang W, Tyrrell H, Ding HT, Pulley J, Boruvka A, Erickson R, Abouhossein M, Ravanello R, Tang MT. Comparable Pharmacokinetics, Safety, and Tolerability of Etrolizumab Administered by Prefilled Syringe or Autoinjector in a Randomized Trial in Healthy Volunteers. Adv Ther. 2021 May;38(5):2418-2434. doi: 10.1007/s12325-021-01661-6. Epub 2021 Mar 29.

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2016
• Primary Completion (Actual): April 9, 2018
• Study Completion (Actual): April 9, 2018

Study Registration Dates

• First Submitted: December 14, 2016
• First Submitted That Met QC Criteria: December 14, 2016
• First Posted (Estimate): December 19, 2016

Study Record Updates

• Last Update Posted (Actual): December 3, 2018
• Last Update Submitted That Met QC Criteria: November 30, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Gastrointestinal Agents; Etrolizumab
• Other Study ID Numbers: GX29504